Related Field
The present invention relates to an improved method for testing materials in vitro. Further it relates to an apparatus for in vitro testing.
Description of Related Art
It is general practise to test biomaterials for implants in two separate ways. Testing of materials is being conducted in two major areas: mechanical testing or characterization of the material itself, i.e. strength, hardness, fatigue, coatings adhesion strength, and biological testing, such as materials biocompatibility, cytotoxicity, bioactivity (e.g. hydroxyapatite growth in vitro), etc. Many biomaterials, including those for implants, are being nowadays tested under different mechanical loading schemes, specified by various standards. Mechanical tests do not usually involve any kind of biological objects. For example, ASTM F2028-02 uses polyurethane as a bone substitute.
Besides conventional (tensile, bending etc.) tests for materials themselves, there are also dedicated test for implant materials such as fatigue tests (e.g. ISO 14801 for dental implants). These tests are targeting on determination of a few parameters only, such as tensile strength, high-cycle fatigue limit, and they are mostly destructive. Their main purpose is to determine the practical limits of materials in service conditions from mechanical point of view only. The most advanced but costly and time-consuming, yet destructive tests are performed at different implant simulators, such as hip simulators, knee simulators, where specific loading patterns are imposed and the wear, fatigue and joint materials degradation is observed. For example, WO 03/009780 discloses the device for fatigue testing of an implantable medical device under compression. For load-bearing implant materials, such as titanium alloys, a typical test is rotating bending fatigue (RBF). WO 2008/022944 discloses fatigue test system for repetitively deforming a tubular implant structure.
Conventional biological tests evaluate biomaterials ability to work in vitro, such as ISO 10993 Parts 3, 5, 9, 12, 14-18. Tests are being carried out in respective culture wells or similar devices with only goal to access the effect of materials (in direct contact or via an extract) on living cells in static conditions. Studies relate to e.g. pharmacological issues (drug elution) and their impact on biological response of the tested material. For example, WO84/03047 discloses an in vitro method for determining the efficacy of therapeutic agents in an artificial capillary or membrane-type cell culturing apparatus. This method is intended for artificial organs (heart, kidney) cytotoxicity analysis.